The research program concerns bile acid synthesis, metabolism and excretion in cholestatic liver disease. For the grant period 6/75 - 5/78 we plan to 1) continue our program on the preoperative diagnostic value of serum bile acids patterns and therapeutic response to phenobarbital and/or cholestyramine; 2) develop a routine screening method for the detection of anicteric neonatal hapatitis; 3) identify the naturally occurring ester sulfates or chenodeoxycholate and other bile acids and prepare and quantitatively estimate their hepatic and renal clearance; 4) using stable isotopes quantitatively evaluate the synthesis rate, in vivo distribution and turnover of mono-, di-, and trihydroxy bile acids in persistent cholestasis with patent bile ducts. Bile acids will be analyzed before and after chemical solvolysis and enzyme or alkaline hydrolysis by thin-layer column and gas-liquid chromatography. Liquid scintillation and mass spectrometry will be used for ratioactive and stable isotopes respectively. Synthesis of conjugated ester sulfates will be done using standard preparative methods. Renal clearance will be done using inulin and p- aminohippurate. The findings should (1) clarify the pathogenesis of extrahepatic biliary atresia and possibly lead to early detection and prevention, and provide more effective management of persistent cholestasis.